This project aims to identify novel small molecule HCV replication inhibitors, ideally with unique mechanism(s) of action. High-throughput screening efforts will be used to identify compounds capable of halting viral replication. Extensive medicinal chemistry efforts will result in compounds with optimized activity and pharmacokinetic parameters. During this period, the project team concluded high-throughput screening efforts, and began medicinal chemistry optimization of hit compounds, leading to the development of several unique chemotypes capable of inhibiting HCV replication. Preclinical pharmacological development is underway to develop compounds with optimized activity, potency, and pharmacokinetics. Advanced characterization studies are also in progress to elucidate likely mechanisms of action for the most promising chemotypes.